Suppression of Peritoneal Metastases by Expression of Murine Endostatin cDNA

Peritoneal seeding is one of problems to be solved in gastrointestinal and ovarian cancers. Angiogenesis is the critical step for a dormancy tumor cluster to be an overt metastatic nodule. However, whether an anti-angiogenesis strategy is effective in the control of peritoneal metastases is still obscure. In this study, we evaluated whether endostatin, an endogenous angiogenesis inhibitor, suppresses peritoneal metastases.

We transduced a human gastric cancer cell line, AGS and a murine renal cancer cell line, Renca, with the plasmid pEndoSTHB, which encodes a secretable form of murine endostatin. Endostatin expression was tested with western blotting, and the biological activity of the secreted endostatin was confirmed with in vitro endothelial cell growth inhibition. In the animal experiments, stable transfectants were injected intraperitoneally.

We demonstrated secretion of endostatin from two cell lines transduced with the plasmid pEndoSTHB. Conditioned media secreted from pEndoSTSB-transduced mammalian cells were shown to potently inhibit endothelial cell growth in vitro. We selected stable transfectants with similar in vitro growth rates of their parental cell lines. Significant tumor growth inhibition was observed in the endostatin-expressing Renca cells intraperitoneal injection group at days of 28, compared to the null transfectants intraperitoneal injection control group.

These results support that peritoneal seeding is angiogenesis-dependant and an anti-angiogenesis strategy is a good way to control peritoneal metastases.